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Age‐associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes—reversal with ( R )‐α‐lipoic acid supplementation

1998; Wiley; Volume: 12; Issue: 12 Linguagem: Inglês

10.1096/fasebj.12.12.1183

1530-6860

Jens Lykkesfeldt, Tory M. Hagen, Vladimir Vinarsky, Bruce N. Ames,

Coenzyme Q10 studies and effects

Ascorbic acid recycling from dehydroascorbic acid and biosynthesis from gulono-1,4-lactone were used as measures of cellular response capacity to increased oxidative stress induced by tert-butylhydroperoxide. The hepatic ascorbic acid concentration was 54% lower in cells from old rats when compared to cells isolated from young rats (P < 0.0005). Freshly isolated hepatocytes from old rats exhibited a significantly decreased ascorbic acid recycling capacity in response to oxidative stress (P < 0.005) compared to cells from young rats. Ascorbic acid synthesis in these cells from old animals was unaffected by various concentrations of tert-butylhydroperoxide, but amounted to only approximately half of the biosynthetic rate when compared to cells from young animals (P < 0.001). Cells from young animals were not significantly affected by the tert-butylhydroperoxide treatments. The results demonstrate a declining ability with age to respond to increased oxidative stress. (R)-α-Lipoic acid, a mitochondrial coenzyme, is a powerful antioxidant. A two-week dietary supplementation of old animals with 0.5% (R)-α-lipoic acid prior to cell isolation almost completely reversed the age-associated effects on ascorbic acid concentration (P <0.0001), recycling (P < 0.05) and biosynthesis after oxidative stress. These results provide further evidence for the potential of α-lipoic acid in treatment of diseases related to oxidative stress. Furthermore, the study extends the value of ascorbic acid as a biomarker of oxidative stress.—Lykkesfeldt, J., Hagen, T. M., Vinarsky, V., Ames, B. N. Age-associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes—reversal with (R)-α-lipoic acid supplementation. FASEB J. 12, 1183–1189 (1998)